EP2584356B9 - Verfahren zur erkennung von urothelkrebs - Google Patents

Verfahren zur erkennung von urothelkrebs Download PDF

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Publication number
EP2584356B9
EP2584356B9 EP11797822.1A EP11797822A EP2584356B9 EP 2584356 B9 EP2584356 B9 EP 2584356B9 EP 11797822 A EP11797822 A EP 11797822A EP 2584356 B9 EP2584356 B9 EP 2584356B9
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EP
European Patent Office
Prior art keywords
ala
ester
urothelial cancer
detecting
fluorescence
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EP11797822.1A
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English (en)
French (fr)
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EP2584356B1 (de
EP2584356A1 (de
EP2584356A4 (de
Inventor
Keiji Inoue
Taro Shuin
Mutsuo Furihata
Yoshihiko Hirao
Tohru Tanaka
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Kochi University NUC
SBI Pharmaceuticals Co Ltd
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Kochi University NUC
SBI Pharmaceuticals Co Ltd
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Publication of EP2584356A4 publication Critical patent/EP2584356A4/de
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Publication of EP2584356B1 publication Critical patent/EP2584356B1/de
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57434—Specifically defined cancers of prostate
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0036—Porphyrins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/34—Genitourinary disorders

Definitions

  • the present invention relates to a method for detecting urothelial cancer, specifically to a method for detecting urothelial cancer using 5-aminolevulinic acid (ALA), a derivative thereof, or a salt of these (hereinafter may be referred to as "ALAs").
  • ALA 5-aminolevulinic acid
  • ALAs a salt of these
  • a diagnostic agent for tumor comprising ALAs is proposed, which agent is intended to determine the presence or absence of tumor in tissues of brain, nasal tract, nasal cavity, trachea, bronchi, buccal cavity, pharynx, esophagus, stomach, breast, colorectum, lung, ovary, central nervous system, liver, bladder, urethra, urinary duct, pancreas, cervical duct, abdominal cavity, anal duct, or cervix uteri, by administering the diagnostic agent for tumor in an amount of 0.001 mg to 10 g per kg of body weight at a time, measuring protoporphyrin IX, uroporphyrin I, coproporphyrin I, etc. in a sample collected in vivo or in vitro such as blood, body fluid, tissue, urine, feces, saliva, sweat, spinal fluid, seminal fluid, or tears to diagnose tumor (see for example Patent Document 2).
  • a PDD cytology method targeting fluorescence exfoliated cells in the urine comprising performing fluorescence cytology and flow cytometry for detecting ALA-induced fluorescence positive cells
  • which method comprises in vitro incubation method comprising dissolving urinary sediment collected from a bladder cancer patient into a serum free culture solution with an ALA concentration adjusted to 200 ⁇ g/mL, and keeping the heat at 37°C for 2 hours in a dark room before subjecting the resultant to the test; and in vivo incubation method subjecting the urinary sediment collected from ALA solution (1.5 g ALA/50 mL buffer) kept in the bladder of a bladder cancer patient for 2 hours to the test (see for example Nonpatent Document 2).
  • the object of the present invention is to provide a method for detecting urothelial cancer that can detect urothelial cancer simply and with high accuracy, without need of a particular culture apparatus, and allowing determination just after urine collection.
  • the present inventors made a keen study with an idea that a technique using ALAs such as described in the above can be applied to cytology of urothelial cancer, and found out that by detecting fluorescence in free cancer cells in the urine excreted from the body of a test subject administered with ALAs, detection of urothelial cancer is possible. Further, they also found out that the dosage amount of ALAs was sufficient in an extremely small amount such as less than a half of the amount used for conventional determination of the excision site. The present invention has been thus completed.
  • the present invention relates to (1) A method for detecting urothelial cancer comprising detecting fluorescence of a cell in urine collected from a test subject orally administered with 5-aminolevulinic acid (ALA), an ester derivative thereof, or a salt of these; (2) a method for detecting urothelial cancer comprising separating a cell from urine collected from a test subject orally administered with 5-aminolevulinic acid (ALA), an ester derivative thereof, or a salt of these, and detecting fluorescence in the separated cell; (3) the method for detecting urothelial cancer according to (1) or (2), wherein the orally administered 5-aminolevulinic acid (ALA), an ester derivative thereof, or a salt of these has been administered in an amount of 0.05 to 20 mg per kg of a test subject in ALA hydrochloride equivalent; (4) the method for detecting urothelial cancer according to any one of (1) to (3), wherein the test subject is a human suspected to have urothelial cancer; the
  • the present invention no particular culture apparatus is needed, and a determination just after urine collection is possible. Further, as it can be determined that there is an abnormality when fluorescence in cells in the urine is detected, it can be immediately transferred to diagnosis through an endoscope or to transurethral resection. For example, by performing the fluorescence detection test in the cells in the urine before an endoscopic examination for determining the presence or absence of relapse, if there is no suspicion, there is no need to go through an endoscopic examination. This significantly reduces burden of patients, which will also lead to reduction of national medical expenses. As such, the method of the present invention allows rapid and simple detection with high accuracy of not only bladder cancer but all urothelial cancers, which is a remarkable technique in the medical services of this field. Further, as the detection is possible with a small dosage amount of ALAs, it is advantageous economically, and there is also an effect in security that photolesion is substantially not caused.
  • the method for detecting urothelial cancer of the present invention is not particularly limited as long as it is a method comprising administering 5-aminolevulinic acid, a derivative thereof, or a salt of these (ALAs) to a test subject, collecting urine from the test subject, and detecting fluorescence in the cells in the collected urine (for example detection of the presence of fluorescence or amount of fluorescence); or a method comprising separating a cell from a urine collected from a test subject administered with 5-aminolevulinic acid, a derivative thereof, or a salt of these (ALAs), and detecting fluorescence in the separated cell.
  • the method for detecting urothelial cancer of the present invention encompasses a method for collecting data for detection.
  • the agent for detecting urothelial cancer of the present invention is not particularly limited as long as it comprises ALAs used in the above-mentioned method of the present invention.
  • the urothelial cancer which is the target of detection in the present invention is a malignant tumor developed from transitional epithelia covering the inner cavity of urinary tract (kidney, renal pelvis, urinary duct, bladder, and urethra).
  • the test subject of the present invention relates to mammals including human, and specifically human being suspected of having urothelial cancer from a medical examination such as medical interview can be exemplified.
  • an ALA derivative is exemplified by those ALAs having an ester group and an acyl group, where the preferred examples include the combinations of methyl ester group and formyl group, methyl ester group and acetyl group, methyl ester group and n-propanoyl group, methyl ester group and n-butanoyl group, ethyl ester group and formyl group, ethyl ester group and acetyl group, ethyl ester group and n-propanoyl group, and ethyl ester group and n-butanoyl group.
  • examples of a salt of ALA or its derivative include: an acid addition salt such as hydrochloride, hydrobromate, hydroiodide, phosphate, nitrate, hydrosulfate, acetate, propionate, toluenesulfonate, succinate, oxalate, lactate, tartrate, glycolate, methanesulfonate, butyrate, valerate, citrate, fumarate, maleate and malate; a metallic salt such as sodium salt, potassium salt and calcium salt; ammonium salt; and alkylammonium salt.
  • these salts are used in the form of a solution and act in a similar manner to ALA and its derivatives.
  • 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester, 5-aminolevulinic acid ethyl ester, 5-aminolevulinic acid propyl ester, 5-aminolevulinic acid butyl ester and 5-aminolevulinic acid pentyl ester, or their hydrochloride, phosphate, hydrosulfate, etc. are preferred.
  • ALAs mentioned above may form a hydrate or a solvate and may be used either alone or in appropriate combination of two or more kinds.
  • the ALAs can be produced by any known method such as production by chemical synthesis, production by microorganisms, and production using enzymes. When producing by microorganisms or using enzymes, it can be used as it is without purification, unless it contains any inconvenient inhibitor.
  • the dosage amount of these ALAs to a test subject is for example 0.02 to 50 mg per 1 kg of a test subject in ALA hydrochloride equivalent, preferably 0.05 to 20 mg, more preferably 0.2 to 10 mg, and furthermore preferably 5 to 10 mg.
  • oral administration including sublingual administration, intravenous administration including drip infusion, transdermal administration using a poultice and the like, suppository, drip infusion, etc. can be exemplified. From the viewpoints of reducing patients' burden or improving sensitivity of fluorescence, oral administration is preferred.
  • the agent for detecting urothelial cancer of the present invention comprising the ALAs can contain, as necessary, other ingredients such as other medicinal ingredients, nutrients, carriers, etc.
  • a carrier that can be blended with the detecting agent of the present invention an organic or inorganic, solid or liquid, pharmacologically acceptable carrier material, which is suitable for intake and is generally inactive, can be used.
  • a carrier include crystalline cellulose, gelatin, lactose, starch, magnesium stearate, talc, vegetable or animal fat, fat and oil, gum and polyalkylene glycol.
  • dosage forms of orally administered agents include powders, granules, tablet, capsule, syrup and suspension.
  • preparations can be produced using a solvent, a disperser, a thickener, an excipient, etc., as appropriate, according to an ordinary method.
  • a solvent a disperser, a thickener, an excipient, etc.
  • the method for detecting urothelial cancer of the present invention allows to detect urothelial cancer by collecting urine after administering ALAs (the detecting agent of the present invention), and detecting the presence or absence of fluorescence or the amount of fluorescence in the cells in the collected urine with a fluorescence microscope, etc. Further, by further adding ALAs to the collected urine, leaving it for a predetermined time according to need, and detecting the presence or absence of fluorescence or the amount of fluorescence, the sensitivity can be further improved.
  • ALAs the detecting agent of the present invention
  • detection (determination) of urothelial cancer can be mechanically performed based on the presence of fluorescence, one without any particular knowledge such as a medical doctor, can easily make the detection. Further, detection can be made using an apparatus.
  • the urine is the first discharged after administering ALAs (the detecting agent of the present invention). It is more preferred to collect urine after 1 hour and within 12 hours after the administration, and more preferably after 2 hours and within 12 hours.
  • the method of taking urine is not limited, and can be from spontaneous urination or collection by catheter.
  • cells are separated from urine by centrifugation or filtration, similarly as for normal cytology.
  • excitation light containing ultraviolet rays comparable to Soret band to visible rays of violet to blue is irradiated, and generated fluorescence is detected with fluorescence microscope, etc.
  • ALA hydrochloride 1 g was dissolved in 50 ml of orange juice, and was given to a patient suspected of having bladder cancer (body weight about 60 kg). Urine was collected after about 4 hours, which was immediately centrifuged (3000 rpm/min., 15 min.) in a light shielded state, and was confirmed by microscopic visualization usingsediments. The results are shown in Fig. 1 .
  • the microscope used was OLYMPUS BX50CCD mounted with camera OLYMPUS DP70.
  • the mirror set was Exciter: XF1076 400AF30 Dichroic:XF2007 475DCLP, Emitter: XF3090 585ALP (OMEGA OPTICAL), all of which being a standard fluorescence microscope system.
  • a clear PPIX fluorescence derived from cancer cell was observed. From a normal pathological diagnosis of the cells, it was shown to be cancer cells.
  • urothelial cancer can be detected by detecting fluorescence of the cells in the urine, without observing in the bladder as in the conventional way.
  • ALAs are supplied to cancer affected areas from blood
  • PPIX derived from ALAs accumulates not only in cancer affected areas but also in cancer cells exfoliated from cancer affected areas.
  • PPIX derived from ALAs were accumulated in cancer cells in the urine exfoliated from cancer affected areas, and an unexpected result was obtained that by detecting fluorescence in the cells in the urine, urothelial cancer can be detected.
  • the detection method was performed in the same way as Example 1, except that the dosage amount was changed to 500 mg, which is the half amount of Example 1. As a result, the picture of Fig. 2 was obtained. From a normal pathological diagnosis of the cells, it was shown to be cancer cells.
  • the method for detecting urothelial cancer of the present invention allows a very rapid, simple and accurate detection with fewer burdens to a patient, and as the dosage amount of ALAs suffices with half of the conventional amount, there is an economic merit. Further, as the risk of vomiting, liver impairment, and photosensitivity which are sometimes observed can be substantially eliminated, it can be said to be a remarkable method that contributes to an early detection of urothelial cancer.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Optics & Photonics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Claims (7)

  1. Verfahren zum Erkennen von Urothelkrebs, umfassend das Erkennen von Fluoreszenz einer Zelle in Urin, der von einem Testsubjekt gesammelt worden ist, welchem oral 5-Aminolevulinsäure (ALA), ein Esterderivat davon oder ein Salz von diesen verabreicht worden ist.
  2. Verfahren zum Erkennen von Urothelkrebs, umfassend das Trennen einer Zelle aus Urin, der von einem Testsubjekt gesammelt worden ist, welchem oral 5-Aminolevulinsäure (ALA), ein Esterderivat davon oder ein Salz von diesen verabreicht worden ist, und Erkennen von Fluoreszenz in der ausgetrennten Zelle.
  3. Verfahren zum Erkennen von Urothelkrebs nach Anspruch 1 oder 2, wobei die oral verabreichte 5-Aminolevulinsäure (ALA), ein Esterderivat davon oder ein Salz von diesen in einer Menge von 0,05 bis 20 mg pro kg eines Testsubjekts in ALA-Hydrochlorid-Äquivalenz verabreicht worden ist.
  4. Verfahren zum Erkennen von Urothelkrebs nach einem der Ansprüche 1 bis 3, wobei das Testsubjekt ein Mensch ist, von dem vermutet wird, dass er an Urothelkrebs leidet.
  5. Verfahren zum Erkennen von Urothelkrebs nach einem der Ansprüche 1 bis 4, wobei das Esterderivat ausgewählt ist aus ALA-Methylester, ALA-Ethylester, ALA-Propylester, ALA-Butylester und ALA-Pentylester.
  6. Gebrauch einer 5-Aminolevulinsäure (ALA), eines Esterderivats davon oder eines Salzes von diesen in dem Verfahren in vitro zum Erkennen von Urothelkrebs nach einem der Ansprüche 1 bis 5.
  7. Gebrauch einer 5-Aminolevulinsäure (ALA), eines Esterderivats davon oder eines Salzes von diesen nach Anspruch 6, wobei das Esterderivat ausgewählt ist aus ALA-Methylester, ALA-Ethylester, ALA-Propylester, ALA-Butylester und ALA-Pentylester.
EP11797822.1A 2010-06-21 2011-06-20 Verfahren zur erkennung von urothelkrebs Active EP2584356B9 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2010140348 2010-06-21
PCT/JP2011/003509 WO2011161933A1 (ja) 2010-06-21 2011-06-20 尿路上皮がんの検出方法

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EP2584356A1 EP2584356A1 (de) 2013-04-24
EP2584356A4 EP2584356A4 (de) 2013-11-27
EP2584356B1 EP2584356B1 (de) 2015-09-16
EP2584356B9 true EP2584356B9 (de) 2016-02-17

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US (1) US9772286B2 (de)
EP (1) EP2584356B9 (de)
JP (1) JP5476613B2 (de)
CN (2) CN106908425A (de)
WO (1) WO2011161933A1 (de)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106908425A (zh) 2010-06-21 2017-06-30 思佰益药业股份有限公司 尿路表皮癌的检测方法
US9488664B2 (en) 2012-01-25 2016-11-08 Sbi Pharmaceuticals Co., Ltd. Diagnostic agent for tumor
LT6038B (lt) * 2012-10-22 2014-06-25 I. Į. Lazerių Ir Bangų Medicinos Mokslinė Klinika Onkologinės patologijos sąlygotų audinių skysčių fotodinaminė diagnostika
US9733187B2 (en) 2015-03-06 2017-08-15 King Saud University Method of detecting bladder cancer by optical analysis of bodily fluids

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Publication number Priority date Publication date Assignee Title
US5079262A (en) * 1989-07-28 1992-01-07 Queen's University At Kingston Method of detection and treatment of malignant and non-malignant lesions utilizing 5-aminolevulinic acid
US7530461B2 (en) * 1995-03-10 2009-05-12 Photocure Asa Esters of 5-aminolevulinic acid as photosensitizing agents in photochemotherapy
JP5034032B2 (ja) 2004-09-29 2012-09-26 Ｓｂｉファーマ株式会社 腫瘍診断剤
EP2272538B1 (de) * 2008-04-22 2020-09-02 SBI Pharmaceuticals Co., Ltd. Verfahren zur erkennung von blasenkrebs
JP2009283902A (ja) * 2008-04-25 2009-12-03 Panasonic Corp 光学デバイスとこれを備えた電子機器
CN106908425A (zh) 2010-06-21 2017-06-30 思佰益药业股份有限公司 尿路表皮癌的检测方法

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US20130095520A1 (en) 2013-04-18
CN106908425A (zh) 2017-06-30
JP5476613B2 (ja) 2014-04-23
WO2011161933A1 (ja) 2011-12-29
CN102918392A (zh) 2013-02-06
JPWO2011161933A1 (ja) 2013-08-19
EP2584356B1 (de) 2015-09-16
EP2584356A1 (de) 2013-04-24
EP2584356A4 (de) 2013-11-27
US9772286B2 (en) 2017-09-26

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